Estrogen Metabolites in the Release of Inflammatory Mediators From Human Amnion-Derived Cells

Barbara Pavan, Guglielmo Paganetto, Alessandro Dalpiaz, Carla Biondi, Laura Lunghi

Life Sci. 2011 Mar 14;88(11-12):551-8.

PMID: 21277863

Abstract:

Aims:




Human amnion-derived cells have been used as in vitro models to test the release of inflammatory mediators, such as arachidonic acid (AA) and prostaglandin E(2) (PGE(2)). We compared estrogen metabolites for their ability to induce AA release, to influence PGE(2) production and to interact toward intracellular estrogen receptors (ERs).













Main methods:




Metabolite effects on AA and PGE(2) release were examined by radiolabelled substrate incorporation and by colorimetric enzyme immunoassays, respectively. [(3)H]17-β-estradiol binding displacements were performed on Ro-20-1724 treated whole cells.













Key findings:




In WISH cells, estrone, 2-hydroxy-estrone and estriol induced a rapid dose dependent release of AA that was not inhibited by cycloheximide. Estrone and 2-hydroxy-estrone showed biphasic dose-response curves of PGE(2), whereas estriol and 16-α-hydroxy-estrone increased PGE(2) levels at high concentrations. 2-methoxy-estrone, 4-hydroxy-estradiol and 4-hydroxy-estrone did not significantly affect PGE(2) release. 2-methoxy-estradiol and 2-hydroxy-estradiol decreased the PGE(2) release. Effects of metabolites on PGE(2) were inhibited by cycloheximide and by the ER antagonist tamoxifen. In AV3 cells PGE(2) production was poorly detectable. On Ro-20-1724 treated WISH cells the K(i) of 17-β-estradiol was 29.2 ± 5.4 nM. Estrone, 2-methoxy-estrone and 2-methoxy-estradiol showed similar affinity values. The hydroxyl substituent at position 2, 4 and 16 decreased or markedly increased the affinity for estradiol or estrone derivatives, respectively.













Significance:




The estrogen metabolites induced nongenomic effects on AA release from WISH cells. The influence on PGE(2) release was detectable only on WISH cells. These effects appeared genomic and mediated by intracellular ERs, whose properties seemed strongly dependent on intracellular cAMP levels.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1241684296-A	Estrone-2,3,4-13C3		1241684-29-6	Price